The natural cytotoxicity receptor NKp46 is dispensable for IL-22-mediated innate intestinal immune defense against Citrobacter rodentium
| Autor: | Christian A. J. Vosshenrich, Ofer Mandelboim, Laure Dumoutier, Vera S. G. Ribeiro, Naoko Satoh-Takayama, Jean-Christophe Renauld, James P. Di Santo, Sarah Lesjean-Pottier |
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| Přispěvatelé: | Vosshenrich, Christian, Cytokines et Développement Lymphoïde, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ludwig Institute for Cancer Research, The Lautenberg Center for General and Tumor Immunology [Jerusalem, Israel], The Hebrew University Hadassah Medical School -BioMedical Research institute Israel Canada of the Faculty of Medicine [Jerusalem, Israel], This work was supported by grants to J.P.D. from the Institut Pasteur, INSERM, and as an 'Equipe Labelisé' by the Ligue Nationale Contre le Cancer. N.S.-T. was the recipient of fellowship from The Uehara Memorial Foundation, Japan., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Nuclear Receptor Subfamily 1
Group F Member 3 MESH: Intestine Small MESH: Spleen [SDV]Life Sciences [q-bio] MESH: Citrobacter rodentium Lymphocyte Activation Interleukin 22 Mice 0302 clinical medicine RAR-related orphan receptor gamma Intestine Small Citrobacter rodentium Immunology and Allergy Antigens Ly MESH: Animals Receptor Cytotoxicity MESH: Enterobacteriaceae Infections 0303 health sciences MESH: Cytokines Enterobacteriaceae Infections MESH: Antigens Ly Nuclear Receptor Subfamily 1 Group F Member 3 3. Good health Cell biology [SDV] Life Sciences [q-bio] DNA-Binding Proteins Killer Cells Natural [SDV.IMM]Life Sciences [q-bio]/Immunology Cytokines MESH: Immunity Innate MESH: Killer Cells Natural MESH: Interleukins [SDV.IMM] Life Sciences [q-bio]/Immunology CD3 MESH: Natural Cytotoxicity Triggering Receptor 1 Immunology Biology 03 medical and health sciences MESH: Mice Inbred C57BL Animals Interleukin-7 receptor MESH: Lymphocyte Activation MESH: Mice 030304 developmental biology Natural Cytotoxicity Triggering Receptor 1 Interleukins Immunity Innate Mice Inbred C57BL biology.protein Cytokine secretion MESH: DNA-Binding Proteins Spleen 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, 2009, 183 (10), pp.6579-6587. ⟨10.4049/jimmunol.0901935⟩ Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, 183 (10), pp.6579-6587. ⟨10.4049/jimmunol.0901935⟩ |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0901935⟩ |
| Popis: | Natural cytotoxicity receptors (including NKp30, NKp44, and NKp46 in humans and NKp46 in mice) are type I transmembrane proteins that signal NK cell activation via ITAM-containing adapter proteins in response to stress- and pathogen-induced ligands. Although murine NKp46 expression (encoded by Ncr1) was thought to be predominantly restricted to NK cells, the identification of distinct intestinal NKp46(+) cell subsets that express the transcription factor Rorc and produce IL-22 suggests a broader function for NKp46 that could involve intestinal homeostasis and immune defense. Using mice carrying a GFP-modified Ncr1 allele, we found normal numbers of gut CD3(-)GFP(+) cells with a similar cell surface phenotype and subset distribution in the absence of Ncr1. Splenic and intestinal CD3(-)NKp46(+) cell subsets showed distinct patterns of cytokine secretion (IFN-gamma, IL-22) following activation via NK1.1, NKp46, IL-12 plus IL-18, or IL-23. However, IL-22 production was sharply restricted to intestinal CD3(-)GFP(+) cells with the CD127(+)NK1.1(-) phenotype and could be induced in an Ncr1-independent fashion. Because NKp46 ligands can trigger immune activation in the context of infectious pathogens, we assessed the response of wild-type and Ncr-1-deficient Rag2(-/-) mice to the enteric pathogen Citrobacter rodentium. No differences in the survival or clinical score were observed in C. rodentium-infected Rag2(-/-) mice lacking Ncr1, indicating that NKp46 plays a redundant role in the differentiation of intestinal IL-22(+) cells that mediate innate defense against this pathogen. Our results provide further evidence for functional heterogeneity in intestinal NKp46(+) cells that contrast with splenic NK cells. The Journal of Immunology, 2009, 183: 6579-6587. |
| Databáze: | OpenAIRE |
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